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Biomedical subjects

C Sweet

Publications and source records attributed to C Sweet.

At least 19 recordsLinked to original sources
PubMed1992

Influenza virus pyrogenicity: central role of structural orientation of virion components and involvement of viral lipid and glycoproteins.

Ultraviolet light-inactivated, non-infectious influenza virus is pyrogenic; virion components are probably responsible for this pyrogenicity. To try to identify the pyrogenic component, influenza virions were disrupted with either bromelain or sodium deoxycholate (DOC). Treatment of infectious virions with bromelain, under conditions that removed the surface glycoproteins (spikes), destroyed their pyrogenicity. The supernatant, containing non-aggregated and modified glycoproteins, was also non-pyrogenic. Disruption of virions with DOC considerably reduced pyrogenicity; however, some was retained by the sub-viral cores. Viral nucleoprotein and matrix protein, purified from the supernatant, were non-pyrogenic. Aggregated stellate clusters of surface glycoproteins separated on sucrose gradients were pyrogenic in half of numerous tests performed with different batches of material. Treatment of virus with ether resulted in complete loss of pyrogenicity. Liposomes made from extracted viral lipid were non-pyrogenic. In contrast, virosomes made from the viral lipid and the aggregated stellate clusters of surface glycoproteins were pyrogenic. Hence, optimum pyrogenicity depends upon the integrity of the virus particle, but haemagglutinin and/or neuraminidase appear essential, and lipid may be involved.

Animals↗
PubMed1991

Exacerbation of bacterial toxicity to infant ferrets by influenza virus: possible role in sudden infant death syndrome.

Of several toxins examined, only staphylococcal alpha and gamma toxin, endotoxin, and diphtheria toxins were lethal for 5-day-old ferrets. Their toxicities were enhanced in animals infected at 1 day old with influenza virus, from 3-fold with staphylococcal gamma toxin through 14-fold for staphylococcal alpha toxin, 84-fold for endotoxin, and 219-fold for diphtheria toxin. No increased viral replication occurred in any tissue; thus the effects of the toxins were exacerbated by the infection, not vice versa. Neonates died suddenly without clinical symptoms as in human babies dying from the sudden infant death syndrome (SIDS). Pathologic examination showed inflammation in the upper respiratory tract, lung edema and collapse, and early bronchopneumonia in the toxin- and influenza virus-treated animals but not in those treated with toxin or virus alone. Thus, bacterial toxins could play a role in SIDS, this being more likely with a concomitant influenza virus infection.

Animals↗
PubMed1991

Virulence of rimantadine-resistant human influenza A (H3N2) viruses in ferrets.

The influence of rimantadine-resistance mutations on the virulence of human H3N2 viruses in ferrets was examined. The similarities in virulence of the drug-resistant mutants with single amino acid substitutions at three different locations, 27, 30, and 31, within the M2 sequence and their corresponding sensitive wild-type isolates contrasted with differences in virulence between the three pairs of viruses. These data provide further evidence that rimantadine-resistant viruses that emerge during treatment of patients with the drug are unaltered both in their growth characteristics and virulence.

Animals↗
PubMed1991

Influenza virus enhancement of membrane leakiness induced by staphylococcal alpha toxin, diphtheria toxin and streptolysin S.

Release of alpha-amino[14C]isobutyric acid from ferret Mpf cells was promoted by staphylococcal alpha toxin, diphtheria toxin and streptolysin S. This release was enhanced to a significant extent if the cells had been previously infected with influenza virus strain A/Puerto Rico/8/34 (PR8, H1N1), although infection with virus alone did not increase the release of radiolabel as compared with that from untreated cells; inactivated virus had a similar enhancing action. The mechanism of enhancement is unclear but it occurs between 0.5 and 2h post-inoculation and viral membrane/endosome membrane fusion is essential. Endotoxin had no effect on membrane permeability, either alone or with PR8. The relevance of these in vitro observations to the previously observed enhancement of toxin lethality by influenza virus in vivo is discussed.

Aminoisobutyric Acids↗
PubMed1991

Nature of the endogenous pyrogen (EP) induced by influenza viruses: lack of correlation between EP levels and content of the known pyrogenic cytokines, interleukin 1, interleukin 6 and tumour necrosis factor.

Fever in influenza results from the release of endogenous pyrogen (EP) following virus-phagocyte interaction and its level correlates with the differing virulence of virus strains. However, the different levels of fever produced in ferrets by intracardial inoculation of EP obtained from the interaction of different virus strains with ferret of human phagocytes did not correlate with the levels of interleukin 1 (IL-1), IL-6 or tumour necrosis factor in the same samples as assayed by conventional in vitro methods. Hence, the EP produced by influenza virus appears to be different to these cytokines.

Animals↗
PubMed1990

Studies on the pathogenicity of a nairovirus, Dugbe virus, in normal and immunosuppressed mice.

Susceptibility to lethal infection with the KT281/75 strain of the tick-borne nairovirus, Dugbe virus, was similar in an outbred strain and several inbred strains of mice. For the outbred strain, both neural and extraneural routes of virus inoculation resulted in lethal infection, but susceptibility decreased with age and only intracerebral inoculation produced a lethal infection in adults. In newborn mice, subcutaneous (s.c.) inoculation of virus (analogous to a tick-bite) produced a disseminated infection, titres being highest in the upper respiratory tract (URT), spleen and liver at 5 days post-inoculation (p.i.), the heart at 7 days p.i. and brain by 8 days p.i. In neonates inoculated intranasally (i.n.), by contrast, virus spread rapidly from the URT to the brain by 2 days p.i., in the absence of a detectable viraemia. Virus was undetectable in the blood of s.c. and i.n. inoculated adults; in the former, virus replication was limited to the site of inoculation, and in the latter virus grew in the respiratory tract and again spread to the brain. Immunosuppression of i.n. inoculated adult mice with cyclophosphamide produced some mortality indicating that host defences are important in protecting the adult, especially as newborn and adult lung tissue were equally able to support the growth of Dugbe virus in culture. The similarity between the pattern of Dugbe virus infection in the mouse and that of other, more pathogenic nairoviruses suggests that, although haemorrhagic disease was not observed, this may be a useful model for studying the genetic basis of nairovirus virulence and for testing vaccines and anti-viral drugs.

Animals↗
PubMed1989

Mechanism of immunity to influenza: maternal and passive neonatal protection following immunization of adult ferrets with a live vaccinia-influenza virus haemagglutinin recombinant but not with recombinants containing other influenza virus proteins.

Neonatal ferrets are protected against infection with influenza virus by milk-derived anti-influenza virus IgG after suckling on an immune mother. Live vaccines protect better than killed vaccines despite their stimulation of lower maternal haemagglutination-inhibiting antibody levels. This suggests that antibody to virus proteins other than the haemagglutinin may also be involved. To investigate this, adult ferrets were immunized intradermally with live vaccinia-influenza virus recombinants each expressing one of the 10 influenza virus polypeptides. Adult ferrets immunized with a recombinant expressing the H3 haemagglutinin were completely protected, and also passively protected their offspring, against a live challenge with clone 7a of the reassortant influenza virus A/Puerto Rico/8/34-A/England/939/69 (H3N2), immunity being mediated by IgG antibody. However, ferrets immunized similarly with recombinants expressing the H1 haemagglutinin, neuraminidase (N1 or N2), polymerases (PB1, PB2 or PAC), matrix protein (M1 or M2), nucleoprotein (NP) or non-structural proteins (NS1 or NS2) were completely susceptible to the influenza virus.

Animals↗
PubMed1989

Isolation and preliminary characterization of temperature-sensitive mutants of mouse cytomegalovirus of differing virulence for 1-week-old mice.

To study the pathogenicity of murine cytomegalovirus (MCMV) and to identify virulence determinants, we have isolated and phenotypically characterized a set of temperature-sensitive mutants. One mutant, PP269/38, was avirulent for 1-week-old BALB/c mice and restricted in its plaque formation and replication at 39 degrees C. Mutants PP242/68 and PP268/38 were 100-fold less virulent than salivary gland-grown virus (SGV), even after two passages in the salivary glands of 1-week-old mice. The former mutant was unable to replicate or form plaques at 39 degrees C whereas the latter replicated poorly at 39 degrees C but not at all at 40 degrees C although it was able to form plaques at 40 degrees C with a reduced plaque size. PP31/15 exhibited a 40-fold reduction in virulence compared to SGV after two passages in vivo and was unable to form plaques or to replicate at 40 degrees C; at 39 degrees C it was able to, with reduced efficiency. The remaining two mutants, PP99/3 and PP392/31, were 10-fold less virulent than SGV and were restricted at 40 degrees C. The six mutants have been classified into at least four complementation groups. These mutants may be useful for studying various aspects of MCMV pathogenicity.

Animals↗
PubMed1988

Role of upper respiratory tract infection in the deaths occurring in neonatal ferrets infected with influenza virus.

Passive immunization of ferret neonates by colostrally-derived anti-influenza virus IgG did not entirely prevent infection when mothers were immunized with 1 or 2 doses of formalin inactivated vaccine with adjuvant (alhydrogel). Influenza virus replication was almost completely prevented in the lower respiratory tract but only slightly reduced in the upper respiratory tract leading to deaths in about 50% of the neonates. Such neonates showed at most only minor lesions in the lower respiratory tract but moderate to severe inflammatory changes in the upper respiratory tract of most animals. This supports previous results suggesting that deaths, reminiscent of the human sudden infant death syndrome (SIDS), may arise purely as a result of upper respiratory tract infection, possibly following obstruction of the airways.

Animals↗
PubMed1979

Comparisons of virulence of influenza virus recombinants in ferrets in relation to their behaviour in man and their genetic constitution.

Two parent viruses, A/Finland/4/74(H3N2) and A/Okuda/57(H2N2), virulent and attenuated respectively for man, showed similar differences of virulence in ferrets as judged by estimations of 50% minimal infectious doses (MID50), the level and persistence of nasal infection, the height and duration of pyrexia and the level of lung infection. In ferrets, two recombinant clones, WRL 94(H3N2) and WRL 105(H3N2), were almost as virulent as A/Finland and indistinguishable from one another, a result which agreed well with genetic analysis (Hay et al. 1977); the RNA pieces of these recombinants appeared identical and largely derived from the virulent parent (A/Finland). The results in ferrets did not agree with tests on clone WRL 94 in small numbers of human volunteers but they were not inconsistent with those on clone WRL 105 in larger numbers. It is possible therefore that careful tests in ferrets may yield more accurate information on the virulence of strains than limited tests in human volunteers. A rapid test for virulence in ferrets is described. It could be used to screen many additional recombinants thereby yielding information on the genetical basis of virulence and indicating possible vaccine strains for more thorough testing in ferrets and in man.

Animals↗
PubMed1979

The localization of influenza virus in the respiratory tract of ferrets: susceptible nasal mucosa cells produce and release more virus than susceptible lung cells.

Infectious virus production by ferret nasal mucosa and lung organ cultures has been monitored in both tissue pieces and medium over 24 h following inoculation with an Asian (H2N2) strain of influenza virus. Freshly prepared cultures of nasal mucosa produced approx. 10-fold more virus per cell than fresh lung cultures. Also the nasal mucosa cells liberated into the medium a greater proportion (mean 31%) of the total virus produced than did fresh lung (mean 6%). Maintenance of lung explants for 24 h prior to inoculation resulted in a 20- to 100-fold increase in the amount of virus released. However, total virus production by fresh and maintained lung was similar. Trypsin did not increase the infectivity of virus released from any of the cultures, indicating that the haemagglutinin in the virus particles was cleaved. Similar results were obtained with a Hong Kong (H3N2) virus strain. Hence, one factor operating in the lower susceptibility of the lung compared with the nasal mucosa in vivo may be a lower capacity of lung cells both to produce and release influenza virus.

Animals↗
PubMed1978

Association of foetal wastage with influenza infection during ferret pregnancy.

Inoculation of influenza virus into pregnant ferrets during the late gestational period was investigated. Foetal resorption followed intracardial inoculation of a large dose of influenza virus (10(9.4) EBID50) and a 100-fold lower dose caused lower litter sizes at birth. The possible role of fever in foetal resorptions was largely discounted by 2 observations: a non-pyrexic dose inoculated intracardially into the pregnant ferret still had detrimental effects on foetal viability; influenza virus inoculated intranasally caused a pyrexia but did not affect the progeny. The potential of the ferret as a model for studying the possible adverse effects of influenza during pregnancy is discussed.

Animals↗
PubMed1978

Sensitivity to pyrexial temperatures: a factor contributing to virulence differences between two clones of influenza virus.

The influence of pyrexia on the differential persistence of a virulent and an attenuated clone of influenza virus in the respiratory tract of ferrets has been further studied. Clone 64d, an attenuated clone of a recombinant virus (A/PR/8/34-A/England/939/69 (H3N2)) grown in organ cultures of ferret nasal turbinates, was inactivated at pyrexial temperatures more readily than a virulent Clone 7a. In addition, replication of Clone 64d was restricted at pyrexial temperatures to a greater extent than that of Clone 7a in organ cultures of both ferret nasal turbinate and lung tissue. The greater adverse effects of pyrexial temperatures on Clone 64d appears to explain the earlier reduction of upper respiratory tract infection seen in ferrets infected with this attenuated clone. Also, the differential influence of pyrexial temperatures may be the reason for the virtual lack of lung infection with Clone 64d in vivo in contrast to the consistent infection found with Clone 7a. The relevance of these findings to human infection and to markers of attenuation of influenza virus is discussed.

Animals↗
PubMed1977

Behaviour in ferrets of swine influenza virus isolated from man.

After intranasal instillation into ferrets, the "swine" influenza virus A/New Jersey/8/76(Hsw1 N1) had a 50% minimal infectious dose similar to that of previously tested A/PR/8-A/England (H3 N2) recombinants virulent and attenuated for man. A/New Jersey produced only a mild upper respiratory tract infection. However, higher titres of virus were recovered from the lungs over a longer period than experienced previously with Asian and Hong Kong virus strains. There was a diphasic pyrexia the second and higher peaks of which correlated with peak titres of virus in lung macerates. These results suggest that A/New Jersey has a pneumotropic potential in ferrets and, if the animal model is valid, possible in man.

Animals↗
PubMed1977

The pregnant guinea-pig as a model for studying influenza virus infection in utero: infection of foetal tissues in organ culture and in vivo.

Organ cultures of guinea-pig foetal tissues showed a similar pattern of susceptibility to influenza virus to that already observed for human (Rosztoczy et al., 1975) and ferret (Sweet, Toms and Smith, 1977) foetal tissues. Respiratory, alimentary and urogenital tract tissues were susceptible whereas neural and lymphopoietic tissues were insusceptible. However, of the foetal membranes (amnion, chorion, umbilical cord and placenta) only the chorion was susceptible, in contrast to the corresponding ferret tissues, all of which were susceptible. The insusceptibility of the placenta paralleled that of human placenta which is similarly haemomonochorial in structure. Following intracardial inoculation of high titre virus (ca 10(9-4) EBID50) into pregnant guinea-pigs virus was isolated from all foetal membranes (amnion, chorion, umbilical cord and placenta), but in low titre. Although sporadic isolations were made from foetal tissues (intestine, kidney, heart, liver and spleen) there was no evidence for viral replication in these tissues. These results are discussed in relation to possible infection of the human foetus in utero with influenza virus.

Animals↗